3β-taraxerol of Mangifera indica, a PI3K dependent dual activator of glucose transport and glycogen synthesis in 3T3-L1 adipocytes

• Published in: Biochimica et biophysica acta. General subjects Vol. 1800; no. 3; pp. 359 - 366
• Main Authors: Sangeetha, Kadapakkam Nandabalan, Sujatha, Sundaresan, Muthusamy, Velusamy Shanmuganathan, Anand, Singaravel, Nithya, Nirmal, Velmurugan, Devadasan, Balakrishnan, Arun, Lakshmi, Baddireddi Subhadra
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.03.2010
• Subjects: 3T3-L1 adipocytes; 3β-Taraxerol; Glucose uptake; Glycogen synthesis; GSK3β; Mangifera indica; PI3K; IRTK; MTT-3-(4,5-Dimethylthiazol-2-yl)-2,5; IRS; Glycogen synthesis; DMEM; LDH; Glucose uptake; PI3K; RT-PCR; 2-DOG; GSK3 β; 3T3-L1 adipocytes; WT; 3β-Taraxerol; NIDDM; NBT; PKB; Mangifera indica; EAE; IRβ; pNPP; GS; Gen; GSK3β; NMR; PTP1B; BCIP; GLUT4; GAPDH
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2009.12.002

The present study focuses on identifying and developing an anti-diabetic molecule from plant sources that would effectively combat insulin resistance through proper channeling of glucose metabolism involving glucose transport and storage. Insulin-stimulated glucose uptake formed the basis for isolation of a bioactive molecule through column chromatography followed by its characterization using NMR and mass spectroscopic analysis. Mechanism of glucose transport and storage was evaluated based on the expression profiling of signaling molecules involved in the process. The study reports (i) the isolation of a bioactive compound 3β-taraxerol from the ethyl acetate extract (EAE) of the leaves of Mangifera indica (ii) the bioactive compound exhibited insulin-stimulated glucose uptake through translocation and activation of the glucose transporter (GLUT4) in an IRTK and PI3K dependent fashion. (iii) the fate of glucose following insulin-stimulated glucose uptake was ascertained through glycogen synthesis assay that involved the activation of PKB and suppression of GSK3β. This study demonstrates the dual activity of 3β-taraxerol and the ethyl acetate extract of Mangifera indica as a glucose transport activator and stimulator of glycogen synthesis. 3β-taraxerol can be validated as a potent candidate for managing the hyperglycemic state.